An important component of respiration Coenzyme Q.sub.10 (2,3-dimethoxy-3-methy-6-decaprenyl-1,4-benzoquinone), also known as ubiquinone, is located in the mitochondria of eukayotes. Coenzyme Q.sub.10 is essential for electron transport, oxidative phosphorylation and it is an effective antioxidant. Experiments have shown that Coenzyme Q.sub.10 is beneficial to organs, including hearts, when supplied orally to whole animals. For example, Folkers et al., Proc. Natl. Acad. Sci. 82:4513 (1985) have shown beneficial results with human hearts after oral consumption of Coenzyme Q.sub.10. Furthermore, isolated organs have benefited from the administration of Coenzyme Q.sub.10 prior to isolation (Sumitomo et al., Surgery 102:821-827 (1987); and Matsushima et al., J. Thorac. Cardiovasc. Surg. 103:945-951 (1992).
Successful organ transplantation is often limited due to ischemic/reperfusion injury. Isolated human hearts deprived of oxygen for more than four hours progressively loose vigor and often do not survive in recipient hosts. Other organs such as the kidney, liver, pancreas and lung are also subject to tissue and cellular damage when removed from their hosts prior to transplantation. This damage is due to hypoxic conditions and a lack of circulation, which normally delivers physiological concentrations of oxygen and nutrients, and removes toxic compounds produced by an organ's cells. Organ transplants have a higher frequency of success when performed immediately after excision from their hosts.
Two recent advances have increased the rate of successful organ transplants and organ surgery, such as coronary bypass surgery. The first includes organ preservation and organ perfusion solutions. The second is improved methods and devices for the delivery of organ perfusion solutions to an organ.
Organs other than hearts can be stored for extended periods prior to transplantation when maintained in an organ preservation solution. Surgery involving organs, such as coronary bypass surgery, requires preservation solutions, i.e., a cardioplegic solution, which help preserve the heart during hypoxic conditions when the heart is stopped. Organ preservation and cardioplegic solutions include Krebs-Henseleit solution, UW solution, St. Thomas II solution, Collins solution and Stanford solution. (See, for example, U.S. Pat. Nos. 4,798,824; 4,938,961; Southard and Belzer, Ann. Rev. Med. 46:235-247 (1995); and Donnelly and Djuric, Am. J. Hosp. Pharm. 48:2444-2460 (1991)).
Organ perfusion devices, such as those described by Sadri (U.S. Pat. Nos. 5,338,662 and 5,494,822), are designed to provide a continuous flow of nutrients, containing physiological concentrations of oxygen, through the vascular tissues of organs including the heart, lung, kidney, liver and pancreas. Drugs and other chemicals can also be delivered to organs using these devices. Perfusion of organs with a perfusion solution provides conditions that more closely resemble the in vivo situation in which organs normally function. Toxic byproducts are flushed from organs by a continuous flow of perfusate solution. Furthermore, organ perfusion can be performed with organs in vitro and in vivo. Therefore, more optimal conditions for organs subjected to transplantation and surgery, such as coronary bypass surgery, are available using an organ perfusion device together with an organ perfusate solution.
Organ perfusion utilizing an organ perfusion device requires a steady flow and delivery of a perfusate solution to an organ. Additives to perfusate solutions, such as drugs, are optimally effective when thoroughly dissolved. Large, undissolved or globular chemical moieties are undesirable in these solutions due to small capillary size and strong shear forces that occur during perfusion through organ tissues. Delivery of highly concentrated chemicals to organs undergoing perfusion, can occur if the chemicals are not dissolved or are aggregated in large particles. Separation or precipitation of the chemical from the perfusion solution while passing through an organ can lead to toxic side effects. Therefore, drugs and other additives to perfusate solutions are best supplied in a soluble form.
Coenzyme Q.sub.10 is insoluble in water, which is the main constituent of organ perfusion and organ preservation solutions. Experiments with whole animals and isolated organs have demonstrated the protective effects of Coenzyme Q.sub.10 and have been conducted with undissolved Coenzyme Q.sub.10, Coenzyme Q.sub.10 dissolved in water-based solutions, and Coenzyme Q.sub.10 dissolved in soybean oil (Folkers et al., Proc. Natl. Acad. Sci. USA 82:4513-4516 (1985); Tatsukawa et al., Life Sci. 24:1309-1314 (19); and Hanioka et al., Molec. Aspects Med. 15:241-248 (1994)). Likewise, isolated organs have been shown to gain protection from ischemia/reperfusion injury when treated with Coenzyme Q.sub.10 (Mori et al. Ann. Thorac. Surg. 39:30-36 (1985)).
However, none of these presentations of Coenzyme Q.sub.10 are appropriate for use with organ perfusion device systems due to the instability of the fatty emulsion leading to the insolubility of Coenzyme Q.sub.10 in water, organ preservation solutions and cardioplegia solutions. In particular, Coenzyme Q.sub.10 can precipitate during perfusion of an organ from the water-based nutrient media during circulation and can be detrimental should insoluble Coenzyme Q.sub.10 crystals block the capillary beds.
Coenzyme Q.sub.10 solubilized in vegetable oil, and the like, is not suitable for use with many organ perfusion devices because the oil can separate from the aqueous phase during passage of perfusate solution through the device. Separated vegetable oil forms large, globular moieties that are undesirable for organ tissues undergoing perfusion. Once the oil separates, Coenzyme Q.sub.10 which can remain, at least partially, dissolved in the oil globules can coat perfusion equipment, including tubing materials, resulting in poor delivery, or the delivery of variable unknown quantities, of Coenzyme Q.sub.10 to the perfused organ. Therefore, it is of vital importance for organs undergoing perfusion that Coenzyme Q.sub.10 be used in a solubilized form that is compatible with organ perfusion systems. The present invention unexpectedly fulfills this and other related needs.